Glycoluril‐Derived Molecular Clips are Potent and Selective Receptors for Cationic Dyes in Water

Molecular clip 1 remains monomeric in water and engages in host–guest recognition processes with suitable guests. We report the K_a values for 32 1? guest complexes measured by ¹H NMR, UV/Vis, and fluorescence titrations. The cavity of 1 is shaped by aromatic surfaces of negative electrostatic potential and therefore displays high affinity and selectivity for planar and cationic aromatic guests that distinguishes it from CBn] receptors that prefer aliphatic over aromatic guests. Electrostatic effects play a dominant role in the recognition process whereby ion–dipole interactions may occur between ammonium ions and the C=O groups of 1 , between the SO₃^? groups of 1 and pendant cationic groups on the guest, and within the cavity of 1 by cation–π interactions. Host 1 displays a high affinity toward dicationic guests with large planar aromatic surfaces (e.g. naphthalene diimide NDI+ and perylene diimide PDI+) and cationic dyes derived from acridine (e.g. methylene blue and azure A). The critical importance of cation–π interactions was ascertained by a comparison of analogous neutral and cationic guests (e.g. methylene violet vs. methylene blue; quinoline vs. N‐methylquinolinium; acridine vs. N‐methylacridinium; neutral red vs. neutral red H⁺) the affinities of which differ by up to 380‐fold. We demonstrate that the high affinity of 1 toward methylene blue (K_a=3.92×10⁷ m ^?1; K_d=25 nm ) allows for the selective sequestration and destaining of U87 cells stained with methylene blue.